Aging is associated with decreases in heart rate, slower atrioventricular (AV) conduction, prolonged cardiac action potentials, reduced cardiac compliance, and slowed diastolic relaxation. Cardiac sensitivity to hormones and the pharmacological agents also changes with age. These phenomena have major implications with respect to cardiovascular pathology in elderly individuals, as well as normal responses to exertion, stress, and medical therapy. To date, the mechanism underlying age-related changes are not well understood. Many of the myocardial functions that are known to be altered by aging depend in some fashion upon transmembrane calcium ion flux. For example, calcium is involved in the initiation and control the heart beat in sinus node cells, in the regulation of conduction through the atrioventricular (AV) node, in the duration of the action potential plateau phase, and in the time required for cardiac muscle contraction and relaxation. Changes in the physiology and/or regulation of voltage- activated calcium channels offers an attractive hypothesis for explaining some or all of the age-related alterations at tissue or whole- animal levels. In this project, we will test the overall hypothesis that calcium channel function is altered in cardiac cells of aging animals. We will also test the subhypotheses that these changes vary in magnitude in different cardiac tissues (myocardium vs. trioventricular node), in different species (rat vs. rabbit), and in different calcium channel subtypes (long-lasting "L-type" vs. transient "T-type"). These studies will be conducted with cells from two aging models: Fisher 344 (F344) rats and New Zealand (NZW) rabbits. Ventricular myocytes and AV nodal cells will be acutely dissociated from mature and senescent animals used in vitro for electrophysiological studies of calcium channels. Recordings will be conducted with the whole-cell patch lamp technique, using pharmacological procedures to isolate voltage-activated calcium channels. Protocols will be applied to assess key biophysical parameters of channel function, including current- voltage relationships, steady-state inactivation, use dependence, and recovery from inactivation. Pharmacological experiments will test sensitivity to calcium channel blockers, an analyze key features of channel blocking such as voltage-dependence and frequency- dependence. These pilot studies will provide the necessary preliminary data for more comprehensive studies of calcium channels in aging cardiac tissues.